tbuckley/cabot-search huggingface dataset:
Evaluating asparaginase toxicity in Hispanic patients with acute lymphoblastic leukemia in a large safety-net hospital.
Authors: Elijah Abdelmeseeh, Marcin Dragon, Sarah Tomassetti
Journal: Journal of Clinical Oncology (2022)

e19012 Background: Asparaginase has been a common component of induction therapy for acute lymphoblastic leukemia (ALL) patients for decades. The use of asaparaginase in the treatment of ALL has shown significant efficacy leading to improved outcomes when used in combination with chemotherapy in children. Despite these results, this medication is not used ubiquitously due to its toxicity profile in adults that includes hepatotoxicity, thrombosis, pancreatitis, and allergic reactions. Established risk factors for increased toxicity are increased age, obesity, and higher doses. Our study aims at reviewing the toxicity profile of this medication in Hispanic patients. We suspected that our patient population will have a higher incidence of various toxicities due to the higher prevalence of obesity and liver disease in this population. Methods: We performed a retrospective chart review of all patients aged greater than 18 years who presented to Harbor-UCLA Medical Center between 2015 and 2021 and were diagnosed with ALL who were given a treatment regimen that included asparaginase. We collected information about demographics, laboratory parameters on diagnosis, treatment details, and information on complications related to the treatment. Results: A total of 14 patients diagnosed with ALL and treated with asparaginase at Harbor-UCLA Medical Center from January 2016-November 2021 were included in this study. Our cohort consists of 53% males and 46% females, with an average age of 31 (SD 9.4). Our patient population had an average of BMI of 34 (SD 8.7), with the majority, 9 out of 14, being classified as obese. The majority of the cohort was Philadelphia chromosome negative (80%). In our study, the incidence of grade 3 to 4 hyperbilirubinemia was 6 out of 14 patients (42%). Half of our patients who suffered from hyperbilirubinemia suffered from class III obesity. The incidence of grade 3 to 4 transaminitis was 13 out of 14 patients (93%). A total of 5 out of 14 patients (36%) also suffered from thrombosis. One patient (7%) had a hypersensitivity reaction. Conclusions: Our incidence of hyperbilirinemia is higher than previously published incidence values. Various studies have shown different incidence rates ranging between 14-40%. Our patient population did experience severe transaminitis in a much higher rate than previously reported rates of around 50%. The higher incidence noted in our patients with class III obesity is in line with recent expert recommendations for dose reduction of asparaginase in patients with severe obesity. We have concluded from our study that our Hispanic population is at higher risk for developing hepatotoxicity after asparaginase use but could be related to the high prevalence of obesity in our population. This is important for future patient care to appropriately select candidates for this intensive therapy and reduce the risk of severe adverse events.
Applying cognitive integration to oncology: A novel asynchronous foundational science curriculum for medical students during clerkships.
Authors: Sam Brondfield, Katherine Hyland, Patricia A. Cornett, Heidi Kirsch
Journal: Journal of Clinical Oncology (2022)

11028 Background: Cognitive integration (CI) connects foundational science (FS) to medical practice and improves clinical reasoning. While evidence supports CI in medical training, the clinical relevance of FS is often obscure to medical students, particularly in oncology, and few learning materials exist to support CI during clerkships. Providing effective and engaging tools to promote CI may enhance understanding of FS relevance to clinical medicine. We therefore aimed to create an online module to integrate FS into clerkships. Methods: Previous student feedback at our institution advocated for clinically relevant FS content. Applying Cognitive Theory of Multimedia Learning principles, we (an oncologist, a biochemist, and an instructional designer) created a cancer module grounded in the hallmarks of cancer (HoC), a key FS principle. To emphasize clinical relevance, we recorded patient interviews incorporating FS. The module, composed in Qualtrics, includes an introduction and four cases, each starting with a brief patient interview, followed by clinical text, images, questions, and explanations. Content co-created by the oncologist and biochemist combined clinical and FS perspectives and referenced the HoC throughout. We piloted a draft with a focus group of four students. The evaluation plan includes written learner feedback, a case-based pre/post-test, and review of clerkship assessments for evidence of CI. Results: We produced an FS oncology module with an estimated engagement time of two hours, which students may complete over multiple sittings. The development team met monthly over the course of one year. Filming and editing cost $100/hour. Overall, the project required approximately 60 faculty person-hours and 12 instructional designer person-hours. The patients interviewed for the module expressed gratitude for sharing their stories with students. The student focus group yielded unanimously positive feedback about the content, the multimedia format, the level of FS covered, and the use of authentic patient videos to enhance clinical relevance. Students strongly preferred this module compared to prior online learning activities. Conclusions: This novel interactive module can serve as a model for development of clerkship curricula promoting CI. Module creation based on real patients resulted in authentic story-telling and enhanced FS relevance. Content development involving a clinician and a basic scientist aligned with CI goals. Limitations include the need for funding and instructional design assistance. A randomized controlled trial comparing a series of novel FS modules to older recorded lectures may demonstrate improved outcomes. Involving learners in curriculum development may decrease faculty burden and increase student interest in FS.
Efficacy and safety of lurbinectedin as second-line therapy in Chinese patients with small cell lung cancer: Preliminary results of a phase 1 study.
Authors: Ying Cheng, Chunjiao Wu, Lulu Chen, Ying Xin, Liang Zhang, Pinghua PAN, Lin Wu, Juan Li, Yanqiu Zhao, Xingya Li, Jun Zhao, Xiaorong Dong
Journal: Journal of Clinical Oncology (2022)

8580 Background: Lurbinectedin (Zepzelca), a selective inhibitor of oncogenic transcription, was granted accelerated approval on June 15, 2020, by the FDA for adult patients (pts) with metastatic small cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy, based on the results from SCLC cohort in PM1183-B-005-14 trial. Here we report the preliminary results of a phase 1 study (LY01017/CT-CHN-101) which aimed to evaluate the safety, tolerability, pharmacokinetics (PK) characters and preliminary efficacy of lurbinectedin in Chinese pts with advanced solid tumors including relapsed SCLC. Methods: In the dose-escalation stage, 10 pts with advanced solid tumors received lurbinectedin (2.5-3.2 mg/m 2 ) as 1-hour i.v. infusion q3wk in a classical 3+3 design, without primary granulocyte colony-stimulating factor (G-CSF) prophylaxis during Cycle 1. In the dose-expansion stage, 22 pts with relapsed SCLC after first-line platinum-based chemotherapy were treated with single-agent lurbinectedin at the recommended dose (RD) defined in the dose-escalation stage, with or without G-CSF support. Endpoints included safety (CTCAE v5.0), tolerability, PK, and confirmed objective response rate (ORR; RECIST v1.1). The data cutoff was January 13, 2022. Results: No dose-limiting toxicity (DLT) was observed in the first 3 pts treated at 2.5 mg/m 2 , while 1/7 pts treated at 3.2 mg/m 2 had DLT (grade 4 neutropenia lasting ≥3 days) in Cycle 1, thus 3.2mg/m 2 without G-CSF prophylaxis was defined as the RD of the dose-expansion stage. At cutoff, 22 SCLC pts treated in the dose-expansion stage were still ongoing, with 21 and 22 pts evaluable for efficacy and safety, respectively. The investigator-assessed confirmed ORR was 42.9% (9/21, partial responses). The duration of response (DOR) is pending. The most common grade 3-4 treatment-related adverse events (TRAEs) were neutropenia (16 [72.7%]), leukopenia (13 [59.1%]), thrombocytopenia (9 [40.9%]), increased ALT (4 [18.2%]), anemia (3 [13.6%]), and increased AST (2 [9.1%]). Serious treatment-related adverse events, including neutropenia (5 [22.7%]), leukopenia (4 [18.2%]), thrombocytopenia (3 [13.6%]), increased ALT (2 [9.1%]), increased AST (2 [9.1%]), vomiting (2 [9.1%]), febrile neutropenia (1 [4.5%]), and edema (1 [4.5%]), were reported in 10 pts (45.5%). No cases of infection, sepsis and Hy’s law were reported. A total of 40.9% (9/22) had dose delay and 31.8% (7/22) had dose reduction, mainly attributed to hematological toxicities. No discontinuations occurred due to AEs. No treatment-related deaths were reported. Conclusions: Lurbinectedin at the RD (3.2mg/m 2 ) shows promising efficacy as second-line therapy in Chinese pts with SCLC, with acceptable tolerability and manageable safety profile. Clinical trial information: NCT04638491.
Efficacy of recombinant Bacillus Calmette-Guérin–dltA in three-dimensional bioprinted bladder cancer-on-a-chip with microfluidic system
Authors: J. Choi, J.H. Kim, J.H. Shim, J.H. Tae, S.Y. Choi, B.H. Chi, T-H. Kim, T.Y. Jung, I.H. Chang
Journal: European Urology (2022)
Response to systemic treatments in advanced fibrolamellar carcinoma: A French multicenter retrospective cohort of the AGEO.
Authors: Xixi Ye-Tran, Mohamed Bouattour, Audrey Perret, Anthony Turpin, Thomas Walter, Carole Vitellius, Romain Coriat, Marie Lequoy, Jean Frederic Blanc, Hélène Regnault, Daniel Pietrasz, David Sefrioui, Thierry Lecomte, Emilie Moati, Olivier Caliez, Eric Nguyen-Khac, Brice Fresneau, Vincent Hautefeuille
Journal: Journal of Clinical Oncology (2022)

e16194 Background: Fibrolamellar carcinomas (FLC) are rare hepatic malignancies affecting young patients without chronic liver disease, often diagnosed at an advanced stage. Few data are available regarding efficacy of systemic anti-tumor treatments. Main objective was to explore response according to RECIST 1.1 criteria in the first line setting in advanced FLC patients. Methods: This retrospective multicentric French cohort included 44 patients with advanced FLC who received at least one systemic treatment and had one morphological evaluation, performed every 2-3 months. Results: Median age at diagnosis was 24 years (range 13-62), 59.1% were female, 38% were at stage IVa (lymph node involvement) and 42% at stage IVb (metastatic involvement). Responses were analyzed in 42 patients, 7 receiving neoadjuvant treatment and 35 patients receiving a first line palliative treatment. There was no complete response, 14.3% (n = 5) had a partial response (PR), 37.1% (n = 13) had stable disease (SD) and 48.6% (n = 17) had progressive disease. GEMOX was the most prescribed regimen (n = 8) with a disease control rate (PR+SD) at 25% (PR = 12.5% and SD = 12.5%). Doxorubicine-platine was the second most prescribed association (n = 5) with a disease control rate at 80% (PR = 40% and SD = 40%). Tyrosine kinase inhibitors, i.e. sorafenib (n = 10) and sunitinib (n = 3) showed no response and a rate of SD of 40% and 33% respectively. The association of doxorubicine-platine plus sorafenib was used in 4 patients, with one PR and three SD. Only one patient received immunotherapy (nivolumab and ipilimumab), but progressed at first evaluation at two months. Median overall survival was 3.3 years. Five years overall survival was 35% (95%CI = 0.23-0.54). Patients who underwent surgery had a better prognosis (55 months vs 15.5 months). Unfortunately, disease relapsed quickly after surgery, with a median relapse-free survival of 11 months. Conclusions: Advanced fibrolamellar carcinomas have a low chemosensitivity to either cytotoxic chemotherapy or tyrosine kinase inhibitors. Larger studies are warranted to define a standard of care for these rare tumors requiring treatment in an expert centre, either with a molecular screening.
Changes in opioid prescription, potential misuse, and substance use disorder in pediatric cancer survivors following the 2016 CDC opioid prescribing guideline.
Authors: Xu Ji, Xin Hu, Katharine Elizabeth Brock, Karen Elizabeth Effinger, Bo Zhang, Joseph Lipscomb
Journal: Journal of Clinical Oncology (2022)

6506 Background: The 2016 Centers for Disease Control and Prevention (CDC) guideline for prescribing opioids, despite not being intended for cancer-related pain, has been shown to be associated with declines in opioid prescriptions among adults with cancer. We examine the changes in opioid prescription, potential misuse, and substance use disorder (SUD) following the guideline release among pediatric cancer survivors, a population at high risk for chronic pain. Methods: Using nationwide private insurance claims data, we identified survivors (aged ≤21 years at cancer diagnosis) who completed treatment for leukemia, lymphoma, central nervous system, bone, or gonadal cancers in 2009-2018 (N=8,969). We also identified enrollees without cancer who were matched based on age, gender, and region as a control group (N=44,845). Outcomes included (1) any opioid prescription and (2) any indicator for potential misuse or SUD within 1-year post-therapy. We conducted interrupted time series analysis, where time period was assessed by quarters based on the quarter-year of patients’ therapy completion. Segmented linear regression was conducted to estimate the immediate change (“level” change) and the change in the time trend (“slope” change) in each outcome after the guideline release in March 2016, accounting for autocorrelation. Results: Before the guideline release, opioid prescription rate (21.1% vs. 7.2%) and rate of potential misuse or SUD (5.6% vs. 1.9%) were higher among survivors than controls ( p&lt;0.05). Post guideline release, we found a declining trend in opioid prescription rate among survivors (slope change = -1.0 percentage point [ppt]; p&lt;0.001). Survivors also experienced an immediate level decrease (-2.0 ppt; p=0.040) and a decreasing trend (slope change = -0.4 ppt; p=0.004) in the rate of potential misuse or SUD. Among controls, there were decreasing trends in opioid prescription rate (slope change = -0.3 ppt; p&lt;0.001) and rate of potential misuse or SUD (slope change = -0.1 ppt; p=0.042). By three years post guideline release, relative reductions in opioid prescription rate and rate of potential misuse or SUD were 51.8% and 76.0%, respectively, among survivors ( p&lt;0.05), with controls experiencing smaller relative reductions (29.4% and 36.5%; p&lt;0.05). Conclusions: Following the release of the CDC opioid prescribing guideline in March 2016, there were reductions in opioid prescription rate and rate of potential opioid misuse or SUD among both pediatric cancer survivors and controls, with survivors experiencing greater reductions.
Early oncologic outcomes of open vs. robot-assisted radical cystectomy with totally intracorporeal urinary diversion: Single centre prospective randomised controlled trial
Authors: R. Mastroianni, G. Tuderti, U. Anceschi, A.M. Bove, A. Brassetti, M. Ferriero, L. Misuraca, S. Guaglianone, M. Gallucci, G. Simone
Journal: European Urology (2022)
Identifying prognostic and predictive value of mutations associated with clinical outcomes in first line (1L) patients with advanced or metastatic non–small cell lung cancer (aNSCLC).
Authors: Diego Perez Parente, Manuel Cobo-Dols, Haroon Hasan, Sara Olson, Navdeep Pal, Samantha Wilkinson, Beatriz La Orden Tévar, Mar Pérez Fernández, Mariano Provencio-Pulla
Journal: Journal of Clinical Oncology (2022)

9047 Background: Whilst the impact of certain mutations on aNSCLC survival outcomes has been evaluated, real-world (rw) evidence on its predictive and prognostic value remains limited. We aimed to identify the predictive and prognostic value of non-driver mutations that are deemed to be clinically relevant in aNSCLC. Methods: This retrospective cohort study analysed de-identified electronic medical records from the Flatiron Clinico-Genomic (FCGD) and FoundationCORE™ databases of aNSCLC patients who have initiated 1L cancer immunotherapy (CIT, alone or in combination) or chemotherapy (chemo) under routine care between 2016 and 2021. Propensity-based multivariable models were used to determine associations between mutational status and progression-free survival (rwPFS), overall survival (rwOS) and overall response (rwR). Results: Of 10,795 patients identified, 2,999 met inclusion criteria (1,042 chemo, 1,957 CIT). Among these, 53% were men and 65% were ≥65 years old. Patients mostly had non-squamous histology (68%), a previous history of smoking (95%) and ECOG ≤1 (61%). 58% of patients were diagnosed as de novo. A total of 185 different mutations were identified in this population, and variants of the same mutation were grouped, identifying 58 mutation families. STK11, KEAP1 and CDKN2A/B mutations were significantly associated with all effectiveness outcomes (Table), indicating lower response (rwR OR&lt;1) and shorter survival (rwOS and rwPFS HR&gt;1) in patients harbouring mutated vs. wild type genes. APC and KRAS mutations were only significantly associated with lower rwR, while FGRF and HRAS mutations were related to worse rwPFS and rwOS, respectively. In contrast, a significantly higher likelihood of response or PFS was associated with ATM/R/RX and GATA3 mutations, respectively. Moreover, our results suggest that KRAS mutations potentially have predictive value for PFS in CIT-treated patients. Mutations with prognostic value on clinical outcomes (overall population). HR, hazard ratio; PFS, progression-free survival; OR, odds ratio; OS, overall survival; rw, real-world. Conclusions: STK11, KEAP1 and CDKN2A/B mutations were significantly associated with poor prognosis in all effectiveness outcomes. In addition, KRAS mutations resulted in clinically significant differences in terms of PFS. Further analyses should be conducted to confirm this clinical significance and to evaluate the relevance of these mutations in future clinical trials design.[Table: see text]
Men’s estimation of life-time risk of receiving a prostate cancer diagnosis, results from the Göteborg-2 prostate cancer screening trial
Authors: E. Palmstedt, M. Månsson, K. Stinesen Kollberg, S. Carlsson, J. Wallström, M. Hellström, J. Hugosson, R. Arnsrud Godtman
Journal: European Urology (2022)
MODL-10. Tumor-brain-organoids as a model for pediatric brain tumors research
Authors: Nicole Riedel, Flavia W De Faria, Carolin Walter, Jan M Bruder, Kornelius Kerl
Journal: Neuro-Oncology (2022)

Abstract BACKGROUND: Embryonal brain neoplasms like atypical teratoid rhabdoid tumor (ATRT) or embryonal tumor with multilayered rosettes (ETMR) still have a very poor outcome despite intensive treatment including chemotherapy, irradiation and surgery. To date, precision oncology has identified clinically relevant innovative therapeutic targets only for a minor subpopulation of pediatric brain tumor patients, which may be due to current in vitro screens not recapitulating the cellular heterogeneity and cellular interactions in vivo. As cellular heterogeneity and cellular interactions majorly influence the response of tumor cells to treatment, we established an innovative 3D screening platform that combines human neural tissue surrounding primary tumor tissue. METHODS: We established a model of tumor-brain-organoids (TBO) by incorporating embryonal tumor cells (ATRT and ETMR tumor cells) into hiPSC-derived forebrain organoids. Using whole mount immunostaining (WMI), we evaluated cancer-phenotype, the neuronal and progenitor cell distribution in brain organoids, and we performed drug screening analysis. Furthermore, we used single-cell RNA-sequencing to characterize the cellular heterogeneity and the effect of tumor-organoid cell-cell communication on transcriptional programs. RESULTS: ATRT as well as ETMR tumor cells incorporated extensively into the organoid tissue. We observed remarkable differences in the invasiveness of ATRT-MYC cells into TBO in comparison with ATRT-SHH and ETMR cells via high content imaging. Moreover, tumor cells affected the gene expression of different cell types of the organoid by upregulating genes of important signaling/growth related pathways (e. g. MAP2K2, IGFBP2) and epigenetic regulators (like BRD7). Screening through a 300 compound FDA-approved drug library in these TBO, we identified potential innovative therapeutic approaches against these embryonal tumors. CONCLUSION: Tumor-brain-organoids can be used as a platform to study tumor biology, tumor interactions with its neural tissue microenvironment, as well as for high-throughput drug and toxicity screening in pediatric brain tumor precision oncology.
Real-world effectiveness of pre-exposure prophylaxis in men at high risk of HIV infection in France: a nested case-control study
Authors: Hugo Jourdain, Sophie Billioti de Gage, David Desplas, Rosemary Dray-Spira
Journal: The Lancet Public Health (2022)

Pre-exposure prophylaxis (PrEP) has shown high efficacy in clinical trials, but few observational studies have confirmed its effectiveness when prescribed in real life to users with diverse profiles. This study aimed to assess real-world PrEP effectiveness.We did a matched, nested case-control study among adult men at high risk of HIV infection between Jan 1, 2016, and June 30, 2020, using data from the French national health data system. Men who were newly diagnosed with HIV infection up to Dec 31, 2020, were individually matched with up to five controls for age, socioeconomic status, place of residence, calendar year, and follow-up duration. PrEP use was characterised on the basis of tenofovir disoproxil fumarate plus emtricitabine dispensing over time. Conditional logistic regression was used to calculate the adjusted odds ratios (ORs) of PrEP use associated with HIV infection. PrEP effectiveness (computed as 1-adjusted OR), was estimated overall, by mode of PrEP use, and by individuals' sociodemographic characteristics.Among a total of 46 706 individuals, 256 patients with HIV infection were identified and matched with 1213 controls. PrEP users accounted for 29% of cases and 49% of controls. PrEP effectiveness was 60% (95% CI 46 to 71) overall, reaching 93% (84 to 97) for a high amount of PrEP consumption, and 86% (78 to 92) if excluding periods after PrEP discontinuation. PrEP effectiveness was significantly reduced in people younger than 30 years (26% [-21 to 54]) and in those who were socioeconomically deprived (-64% [-392 to 45]), both of which groups showed low amounts of PrEP consumption and high rates of PrEP discontinuation.PrEP effectiveness appears to be lower in real-world conditions than is reported in clinical trials. Strengthening efforts to improve the monitoring of PrEP compliance will be essential to ensure PrEP effectiveness, especially among young and socioeconomically deprived recipients.None.